Anxiety and depression are the two most common mental health disorders, impacting ˜25% of the US population per year (Kessler et al., 2005). While the treatment of affective disorders has improved substantially since the introduction of drugs such as selective monoaminergic reuptake inhibitors, one-third of individuals with these disorders remain treatment resistant (Trivedi et al., 2006). Furthermore, adverse side effects of these drugs limit their use in some patients. These issues with conventional pharmacotherapy for affective disorders underscore the need for drugs aimed at new targets for the treatment anxiety and depression. Neuronal nicotinic acetylcholine receptors (nAChRs) may be one such target.
The enhancement of GABAergic and monoaminergic neurotransmission has been the mainstay of pharmacotherapy and the focus of drug discovery for anxiety and depressive disorders for several decades. However, the significant limitations of drugs used for these disorders underscore the need for novel therapeutic targets. Neuronal nicotinic acetylcholine receptors (nAChRs) may represent one such target. For example, nicotine elicits anxiolytic effects in rodent models, and mecamylamine, a non-competitive antagonist of nAChRs, displays positive effects in preclinical tests for anxiolytic and antidepressant activity in rodents.